祖父江 嘉洋

AIMS: Sudden cardiac death (SCD) is a common mode of death in patients with congestive heart failure (CHF). Implantable cardioverter defibrillator (ICD) implantation is established treatment for SCD prevention, but current eligibility criteria based on left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class may be due for reconsideration given the increasing effectiveness of pharmacological therapy. We sought to reconsider the risk stratification of SCD in patients with symptomatic CHF. METHODS: In total, 1,676 consecutive patients (74 ± 13 years old; 56% male) with NYHA class II or III CHF between 2008 and 2015 were enrolled for this prospective study. The endpoint was SCD. RESULTS: During a median (interquartile range) follow-up period of 25 (4-70) months, 198 (11.8%) patients suffered SCD. Of those events, 23% occurred within 3 months of discharge. In the adjusted analyses, estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11-2.70, P = 0.01] and LVEF ≤ 35% (HR 2.31, 95% CI 1.47-3.66, P < 0.01) were independent risk predictors of SCD. Addition of eGFR to LVEF significantly improved prediction of SCD in the C-index (P = 0.04), and in two metrics, net reclassification improvement (P = 0.01) and integrated discrimination improvement (P = 0.03). The predictive power of eGFR declined time-dependently over 2 years. CONCLUSIONS: The addition of eGFR to current eligibility criteria may be useful for risk assessment of SCD, although its predictive power wanes over time. Roughly a quarter of the SCD occurred within 3 months after discharge in patients with CHF.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

BACKGROUND: We aimed to investigate the association between ventricular repolarization instability and sustained ventricular tachycardia and ventricular fibrillation (VT/VF) occurring within 48 h (acute-phase VT/VF) after the onset of acute coronary syndrome (ACS) and the prognostic role of repolarization instability and heart rate variability (HRV) after discharge from the hospital. METHODS: We studied 572 ACS patients with a left ventricular ejection fraction >35%. The ventricular repolarization instability was assessed by the beat-to-beat T-wave amplitude variability (TAV) using high-resolution 24-h Holter ECGs recorded at a median of 11 days from the date of admission. We calculated the HRV parameters including the deceleration capacity (DC) and non-Gaussian index calculated on a 25 s timescale (λ25s). The DC and λ25s were dichotomized based on previous studies' thresholds. RESULTS: Acute-phase VT/VF developed in 43 (7.5%) patients. In-hospital mortality was significantly higher among VT/VF patients (4.7% vs. 0.9%, p = .03). An adjusted logistic model showed that the maximum TAV (odds ratio 1.02, 95% confidence interval [CI] 1.00-1.29, p = .04) was associated with acute-phase VT/VF. During a median follow-up period of 2.1 years, 19 (3.3%) patients had cardiac deaths or resuscitated cardiac arrest. Acute-phase VT/VF (p = .12) and TAV (p = .72) were not significant predictors of survival. An age and sex-adjusted Cox model showed that the DC (p < .01), λ25s (p < .01), and emergency coronary intervention (p < .01) were independent predictors. CONCLUSION: T-wave amplitude variability was associated with acute-phase VT/VF, but the TAV was not predictive of survival post-discharge. The DC, λ25s, and emergency coronary intervention were independent predictors of survival.

OBJECTIVE: The early detection of cardiac disease is important because the disease can lead to sudden death and poor prognosis. Electrocardiograms (ECG) are used to screen for cardiac diseases and are useful for the early detection and determination of treatment strategies. However, the ECG waveforms of cardiac care unit (CCU) patients with severe cardiac disease are often complicated by comorbidities and patient conditions, making it difficult to predict the severity of further cardiac disease. Therefore, this study predicts the short-term prognosis of CCU patients to detect further deterioration in CCU patients at an early stage. METHODS: The ECG data (II, V3, V5, aVR induction) of CCU patients were converted to image data. The transformed ECG images were used to predict short-term prognosis with a two-dimensional convolutional neural network (CNN). RESULTS: The prediction accuracy was 77.3%. Visualization by GradCAM showed that the CNN tended to focus on the shape and regularity of waveforms, such as heart failure and myocardial infarction. CONCLUSION: These results suggest that the proposed method may be useful for short-term prognosis prediction using the ECG waveforms of CCU patients. CLINICAL IMPACT: The proposed method could be used to determine the treatment strategy and choose the intensity of treatment after admission to the CCU.

BACKGROUND: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). METHODS: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. RESULTS: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). CONCLUSION: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

Contrast-associated acute kidney injury (CA-AKI) is a complication of percutaneous coronary intervention (PCI). Because proteinuria is a sentinel marker of renal dysfunction, we assessed its role in predicting CA-AKI in patients undergoing PCI. A total of 1,254 patients undergoing PCI were randomly assigned to a derivation (n = 840) and validation (n = 414) dataset. We identified the independent predictors of CA-AKI where CA-AKI was defined by the new criteria issued in 2020, by a multivariate logistic regression in the derivation dataset. We created a risk score from the remaining predictors. The discrimination and calibration of the risk score in the validation dataset were assessed by the area under the receiver-operating characteristic curves (AUC) and Hosmer-Lemeshow test, respectively. A total of 64 (5.1%) patients developed CA-AKI. The 3 variables of the risk score were emergency procedures, serum creatinine, and proteinuria, which were assigned 1 point each based on the correlation coefficient. The risk score demonstrated a good discriminative power (AUC 0.789, 95% CI 0.766-0.912) and significant calibration. It was strongly associated with the onset of CA-AKI (Cochran-Armitage test, p < 0.0001). Our risk score that included proteinuria was simple to obtain and calculate, and may be useful in assessing the CA-AKI risk before PCI.

BACKGROUND: Left-ventricular systolic dysfunction (LVSD) comorbid with atrial fibrillation is reversible, but recovery is limited in a subset of patients. The Selvester QRS (S-QRS) score is an electrocardiogram-based assessment that reportedly reflects myocardial scar/damage. We evaluated the predictability of S-QRS score for the recovery of left-ventricular ejection fraction (LVEF) in persistent AF (PeAF) patients with LVSD undergoing catheter ablation (CA). METHOD: CA was performed in 51 PeAF patients with reduced LVEF (<40%); S-QRS scores were measured after restoration of sinus rhythm. LVEF was re-evaluated at one year after CA; LVEF recovery was related to the S-QRS score. RESULTS: The median [interquartile range] S-QRS score was 1 point [0-2]. LVEF increased from 32% [28-37] at baseline to 56% [49-57] at 1 year after CA. Thirty-seven patients achieved normalization of LVEF (≥50%, Group A); 14 patients did not (Group B). Group A had significantly lower S-QRS scores than Group B (0 point [0-2] vs. 2 points [2-3], p < .05). In univariate/multivariate analyses, S-QRS score was an independent predictor of LVEF normalization. In the receiver operating characteristic curve, the cut-off value of S-QRS score was 2 points for prediction of the LVEF normalization (AUC = 0.79). Patients with low S-QRS score (<2 points) had greater LVEF improvement than those with high S-QRS score (≥2 points, ΔLVEF: 23% [17-28] vs. 17% [12-24], p < .05). CONCLUSION: S-QRS scoring noninvasively assesses the improvement of LVEF in PeAF patients with LVSD after CA. A high S-QRS score may indicate underlying myocardial scar/damage associated with unknown etiologies for LVSD other than PeAF.

BACKGROUND: Telerehabilitation is an alternative clinic-based rehabilitation. A remote monitoring (RM) system attached to a cardiac rhythm device can collect physiological data and the device function. This study aimed to evaluate the safety and feasibility of telerehabilitation supervised by an RM in patients receiving cardiac resynchronization therapy (CRT). METHODS: A single group pre-post exercise program was implemented for 3 months in 18 CRT recipients. The exercise regimen consisted of walking a prescribed number of steps based on a 6-min walk distance (6MWD) achieved at baseline. The patients were asked to exercise 3 to 5 times per week for up to 30 min per session, wearing an accelerometer to document the number of steps taken. The safety was assessed by the heart failure hospitalizations and all-cause death. The feasibility was measured by the improvement in the quality of life (QOL) using the EuroQol 5 dimensions, and daily active time measured by the CRT, 6MWD, B-type natriuretic peptide (BNP) level, and left ventricular ejection fraction (LVEF). RESULTS: No patients had heart failure hospitalizations or died. No patients had any ventricular tachyarrhythmias. One patient needed to suspend the exercise due to signs of exacerbated heart failure by the RM. Compared to baseline, there were significant improvements in the QOL (-0.037, p < .05), active time (1.12%/day, p < .05), and 6MWD (11 m, p < .001), but not the BNP (-32.4 pg/ml, p = .07) or LVEF (0.28%, p = .55). CONCLUSIONS: Three months of RM-guided walking exercise in patients with CRT significantly increased the QOL, active time, and exercise capacity without any adverse effects.

BACKGROUND: Myocardial perfusion imaging (MPI) and fractional flow reserve (FFR) are established approaches to the assessment of myocardial ischemia. Recently, various FFR cutoff values were proposed, but the diagnostic accuracy of MPI in identifying positive FFR using various cutoff values is not well established.Methods and Results:We retrospectively studied 273 patients who underwent stress MPI and FFR within a 3-month period. Results for FFR were obtained from 218 left anterior descending artery (LAD) lesions and 207 non-LAD lesions. Stress MPI and FFR demonstrated a good correlation in the detection of myocardial ischemia. However, the positive predictive value (PPV) of FFR for detecting MPI-positive lesions at the optimal FFR thresholds was insufficient (44% for LAD and 65% for non-LAD lesions). This was caused by a sharp drop in PPV at an FFR threshold of 0.7 or more. Notably, 41% of the lesions with normal MPI demonstrated FFRs <0.80. However, MPI-negative lesions had an extremely low lesion rate with FFR <0.65 (6%). Conversely, 78% and 41% of MPI-positive lesions had FFR <0.80 and <0.65, respectively. CONCLUSIONS: The data confirmed that decisions based on MPI are reasonable because MPI-negative patients have an extremely low rate of lesions with a FFR below the cutoff point for a hard event, and MPI-positive lesions include many lesions with FFR <0.65.

BACKGROUND. For clinical decision making, it was recently recommended that values of fractional flow reserve (FFR) derived from coronary CTA (FFRCT) be measured 1-2 cm distal to the stenosis, given the potential for overestimation of ischemia when FFRCT values at far distal segments are used. Supporting data are, however, lacking. OBJECTIVE. The purpose of the present study was to evaluate the diagnostic performance of FFRCT values measured 1-2 cm distal to the stenosis and at more distal locations relative to invasive FFR values. METHODS. FFRCT and invasive FFR values for 365 vessels in 253 patients identified from the Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care (ADVANCE) registry were prospectively assessed. FFRCT values were measured 1-2 cm distal to the stenosis and at the pressure wire position and far distal segments. The diagnostic accuracy of FFRCT was assessed on the basis of the ROC AUC. The AUC of FFRCT was calculated using FFRCT as an explanatory variable and an invasive FFR of 0.80 or less as the dichotomous dependent variable. RESULTS. The AUC of FFRCT values measured 1-2 cm distal to the stenosis (0.85; 95% CI, 0.80-0.88) was higher (p = .002) than that of FFRCT values measured at far distal segments (0.80; 95% CI, 0.76-0.84) and similar (p = .16) to that of FFRCT values measured at the pressure wire position (0.86; 95% CI, 0.81-0.89). FFRCT values measured 1-2 cm distal to the stenosis and at far distal segments had sensitivity of 87% versus 92% (p = .003), specificity of 73% versus 42% (p < .001), PPV of 75% versus 59% (p < .001), and NPV of 86% versus 85% (p = .72), respectively. Subgroup analyses of lesions of the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery all showed improved specificity and PPV (all p < .005) for FFRCT values measured 1-2 cm distal to the stenosis compared with values measured at the pressure wire position. However, the AUC was higher for measurements obtained 1-2 cm distal to the stenosis versus those obtained at far distal segments, for left anterior descending coronary artery lesions (p < .001) but not for left circumflex coronary artery lesions (p = .27) or right coronary artery lesions (p = .91). CONCLUSION. The diagnostic performance of FFRCT values measured 1-2 cm distal to the stenosis was higher than that of FFRCT values measured at far distal segments and was similar to that of FFRCT values measured at the pressure wire position in evaluating ischemic status, particularly for left anterior descending coronary artery lesions. CLINICAL IMPACT. The present study supports recent recommendations from experts to use FFRCT measured 1-2 cm distal to the stenosis, rather than measurements obtained at far distal segments, in clinical decision making.

The diastolic pressure ratio (dPR) and resting full-cycle ratio (RFR) are considered to be almost identical to the instantaneous wave-free ratio (iFR) in the retrospective analysis of pooled data. The aim of this study was to investigate the direct comparison of iFR and these new resting indexes in real world practice. Two pressure wires were inserted and placed in the distal part of the same coronary artery. The measurement of the iFR and the other resting indexes was performed simultaneously. A total of 54 lesions from 23 patients were subject to physiological study. In 49 lesions, iFR and other resting indexes were also measured in hyperemic conditions. The general correlation between iFR and other resting indexes was excellent in both resting and hyperemic conditions (r2 = 0.99; mean difference - 0.001 ± 0.021; p < 0.001; and r2 = 0.99; mean difference - 0.012 ± 0.025; p < 0.001, respectively). This correlation was maintained in various subgroup analyses. A diagnostic change between iFR and other resting indexes occurred in three cases (3%) when a fixed cut-off point (≤ 0.89) was applied. There was no diagnostic change when a hybrid zone (0.86 ≤ iFR ≤ 0.93) was considered. The new resting indexes and iFR showed very high correlation in real world practice. A diagnostic change only occurred in three cases (3%) when a fixed cut-off point (≤ 0.89) was applied.

There are few reports on the coexistence of cardiac amyloid light-chain (AL) amyloidosis and light chain deposition disease (LCDD), despite their similar pathophysiologies caused by plasma-cell dyscrasia. Herein, we report the coexistence of these diseases. A 59-year-old man was referred to our hospital because of exertional dyspnea and hypotension. Renal dysfunction of unknown etiology had been present for 4 years and hemodialysis had been introduced. Severe systolic and diastolic cardiac dysfunction was apparent, accompanied with dilatation and granular sparkling, but not with left ventricular hypertrophy. The plasma-free light chain κ was found to be extremely high, with a κ/λ ratio of 1,919. Light microscopic examination of the endomyocardial biopsy revealed spotty and homogenous deposits, which positively stained with Congo red, and exhibited a blazing apple-green color under polarized light. Based on these results, cardiac amyloidosis was diagnosed. In specimens prepared for electron microscopy, no amyloid fibrils could be found. Instead, we observed amorphous nonfibrillar deposits around several small vessels including capillaries and small arteries, which were consistent with light-chain deposits. LCDD was diagnosed based on the systemic increase in κ light chain and the ultrastructural findings of the endomyocardial biopsy specimens. Coexistence of cardiac amyloidosis and LCDD was thus confirmed in our patient. An electron microscopic assessment in addition to Congo red staining may be useful to diagnose latent LCDD in patients with suspected cardiac light-chain amyloidosis.

OBJECTIVES: The aim of this study was to investigate the accuracy of pre-percutaneous coronary intervention (PCI) predicted nonhyperemic pressure ratios (NHPRs) with actual post-PCI NHPRs and to assess the efficacy of PCI strategy using pre-PCI NHPR pullback. BACKGROUND: Predicting the functional results of PCI is feasible using pre-PCI longitudinal vessel interrogation with the instantaneous wave-free ratio (iFR), a pressure-based, adenosine-free NHPR. However, the reliability of novel NHPRs (resting full-cycle ratio [RFR] and diastolic pressure ratio [dPR]) for this purpose remains uncertain. METHODS: In this prospective, multicenter, randomized controlled trial, vessels were randomly assigned to receive pre-PCI iFR, RFR, or dPR pullback (50 vessels each). The pre-PCI predicted NHPRs were compared with actual NHPRs after contemporary PCI using intravascular imaging. The number and the total length of treated lesions were compared between NHPR pullback-guided and angiography-guided strategies. RESULTS: The predicted NHPRs were strongly correlated with actual NHPRs: iFR, r = 0.83 (95% confidence interval: 0.72 to 0.90; p < 0.001); RFR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001), and dPR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001). The number and the total length of treated lesions were lower with the NHPR pullback strategy than with the angiography-guided strategy, leading to physiological improvement. CONCLUSIONS: Predicting functional PCI results on the basis of pre-procedural RFR and dPR pullbacks yields similar results to iFR. Compared with an angiography-guided strategy, a pullback-guided PCI strategy with any of the 3 NHPRs reduced the number and the total length of treated lesions. (Study to Examine Correlation Between Predictive Value and Post PCI Value of iFR, RFR and dPR; UMIN000033534).

Background: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is an established tool for identifying lesion-specific ischemia that is now approved for use by the Japanese insurance system. However, current clinical reimbursement is strictly limited to institutions with designated appropriate use criteria (AUC). This study assessed differences in physicians' behavior (e.g., use and interpretation of FFRCT, final management) according to Japanese AUC and non-AUC site designation. Methods and Results: Of 5,083 patients in the ADVANCE Registry, 1,829 from Japan were enrolled in this study. Physicians' behavior after interrogating CCTA and FFRCT was analyzed separately according to AUC and non-AUC site designation. Compared with AUC sites, patients referred for FFRCT from non-AUC sites had a higher rate of negative FFRCT, less severe anatomic stenosis, and a slightly lower rate of management plan reclassification (51.2% vs. 61.3%), with near-identical utility in both groups. Actual care corresponded equally well to post-FFRCT plans in both groups. The likelihood of revascularization for positive or negative FFRCT was similar between the 2 groups. Importantly, AUC and non-AUC sites were equally unlikely to revascularize patients with negative FFRCT and stenosis >50% or patients with positive FFRCT and stenosis <50%. Conclusions: Compared with AUC sites, non-AUC sites had lower disease burden and reclassification of management plans, but nearly identical clinical integration. Actual care corresponded equally well to post-FFRCT recommendations at both sites.

OBJECTIVES: The aim of this study was to compare diagnostic performance between quantitative flow ratio (QFR) derived from coronary angiography and fractional flow reserve derived from computed tomography (FFRCT) using fractional flow reserve (FFR) as the reference standard. BACKGROUND: QFR and FFRCT are recently developed, less invasive techniques for functional assessment of coronary artery disease. METHODS: QFR, FFRCT, and FFR were measured in 152 patients (233 vessels) with stable coronary artery disease. RESULTS: QFR was highly correlated with FFR (r = 0.78; p < 0.001), whereas FFRCT was moderately correlated with FFR (r = 0.63; p < 0.001). Both QFR and FFRCT showed moderately good agreement with FFR, presenting small values of mean difference but large values of root mean squared deviation (FFR-QFR, 0.02 ± 0.09; FFR-FFRCT, 0.03 ± 0.11). The sensitivity, specificity, positive predictive value, and negative predictive value of QFR ≤0.80 for predicting FFR ≤0.80 were 90%, 82%, 81%, and 90%, respectively. Those of FFRCT ≤0.80 for predicting FFR ≤0.80 were 82%, 70%, 70%, and 82%, respectively. The diagnostic accuracy of QFR ≤0.80 for predicting FFR ≤0.80 was 85% (95% confidence interval [CI]: 81% to 89%), whereas that of FFRCT ≤0.80 for predicting FFR ≤0.80 was 76% (95% CI: 70% to 80%). CONCLUSIONS: QFR and FFRCT showed significant correlation with FFR. Mismatches between QFR and FFR and between FFRCT and FFR were frequent.

OBJECTIVES: The objective was to evaluate the safety, feasibility, and accuracy of the jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure dilatation using a non-compliant balloon after main vessel stenting. BACKGROUND: Fractional flow reserve (FFR) information can help interventionists determine whether they should treat a jailed-side branch (SB). However, re-crossing a pressure wire into a jailed-SB is sometimes technically difficult. METHODS: Fifty-one consecutive lesions from 48 patients who underwent the jailed-pressure wire technique were retrospectively investigated. The primary endpoint was complication rate and secondary endpoints included success rate of FFR measurement, incidence of wire disruption, and final drift rate. The usability of FFR for percutaneous coronary intervention of coronary bifurcation lesion was also evaluated. RESULTS: Median age of the patients was 69 years and 80.4% were men. The most frequent underlying disease was stable angina (70.6%) and 68.6% were type B2 lesions. Our main findings were: the procedure was performed successfully in all cases without any complications or wire disruption, FFR could be measured without significant final drift in 95.9% of cases, and FFR measurements helped interventionists determine whether to perform a final kissing balloon dilatation in 49.0% cases. CONCLUSIONS: The jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure post-dilatation maneuver was safe, feasible, and accurate.

BACKGROUND: This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 mTc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 mTc-tetrofosmin/stress 201Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols. CONCLUSIONS: The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.

Heart failure (HF) is classified into three clinical subtypes: HF with a preserved ejection fraction (HFpEF: EF ≥ 50%), HF with a mid-range ejection fraction (HFmrEF: 40 ≤ EF < 49%), and HF with a reduced ejection fraction (HFrEF: EF < 40%). These types often coexist with atrial fibrillation (AF). We investigated the rate of strokes/systemic embolisms (SSEs) in AF patients with HFpEF (AF-HFpEF) compared to that in those with HFrEF (AF-HFrEF: HFmrEF and HFrEF), and examined the independent predictors. We prospectively enrolled 1350 patients admitted to our hospital for worsening HF. We identified 301 patients with either AF-HFpEF (n = 129, 43%) or AF-HFrEF (n = 172, 57%). Compared to the patients with AF-HFrEF, those with AF-HFpEF were older and more likely to be female. Oral anticoagulant use was 63 vs. 66%, respectively. During a mean follow-up period of 26 months, 21 (7%) and 66 (22%) patients had SSEs and all-cause death, respectively. The crude annual rates of SSEs (3.9 vs. 2.7%, P = 0.47) were similar between the groups. In a multivariate Cox regression analysis, an age ≥ 75 years (hazard ratio 2.14, 95% confidence interval 1.32-3.58, P < 0.01) and the plasma B-type natriuretic peptide (BNP) level ≥ 341 pg/ml (hazard ratio 1.60, 95% confidence interval 1.07-2.39, P < 0.05) were associated with SSEs. The EF was not an independent predictor of SSEs (hazard ratio 1.01, 95% confidence interval 0.98-1.04, P = 0.51). There were no significant differences in the rates of SSEs between AF-HFpEF and AF-HFrEF. Patients with HF and concomitant AF should be treated with anticoagulants irrespective of EF.

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and is associated with morbidity and mortality. Over the past 2 decades, there have been major advances in understanding AF pathophysiology, but important knowledge gaps, particularly about targetable basic mechanisms, remain. Recent metabolomic and proteomic studies have shown changes in the expression of molecules involved in metabolic pathways in human and experimental AF, indicating a role for metabolic alterations in AF pathophysiology. AF is characterized by irregular high-frequency excitation and contraction that affect atrial energy demands, circulation and oxygen supply, and change the balance between metabolic demand and supply, causing metabolic stress. Here, we review the information available about AF-induced metabolic changes and their pathophysiological contribution. We also discuss the possibilities of developing novel therapeutic strategies that act by modulating cardiac metabolic processes during AF.

BACKGROUND: Takotsubo cardiomyopathy (TC) is a myopathy triggered by severe stressful events. However, little is known about the determinants of in-hospital outcomes. We prospectively determined the effect of different triggers on the prognosis of TC. METHODS AND RESULTS: We enrolled patients who were admitted for suspected acute coronary syndrome (ACS) from January 2008 to December 2015. TC was diagnosed according to the Mayo Clinic diagnosis criteria. The outcome was in-hospital death. Among 1861 consecutive patients with suspected ACS, 82 (4.4%) patients were diagnosed with TC. There were 43 patients (52%) with physical triggers (Physical), 26 (31%) with emotional triggers, and 13 (17%) with no identifiable triggers. The latter two groups were combined and categorized as the Non-physical trigger group. Compared with non-physical triggered TC, patients with physical triggered TC were more likely to have a malignancy (p=0.008), lower blood pressure (p=0.001), lower hemoglobin (p<0.001), higher serum creatinine (p<0.001) and higher norepinephrine levels (p=0.007). During a mean hospital stay of 16±12days, 9 (20.9%) of the Physical and 1 (2.6%) of the Non-physical patients died in-hospital (log-rank p=0.007). After adjusting for the age, gender, trigger, malignancy, and hemoglobin level, being male (hazard ratio 11.9, 95% confidence interval, 2.43-58.5, p=0.002) and having a physical trigger (14.7, 1.19-166, p=0.03) were associated with in-hospital mortality. CONCLUSION: There was a significant difference in in-hospital mortality depending on the trigger type in TC. Being male and having a physical trigger were independent risk factors of in-hospital mortality from TC.

AIMS: Premature ventricular complexes (PVCs) originating from the right ventricular outflow tract (RVOT) may occasionally trigger monomorphic ventricular tachycardia (MVT), polymorphic ventricular tachycardia (PVT), or ventricular fibrillation (VF). We examined whether an analysis of the ventricular repolarization instability could differentiate PVT/VF triggered by RVOT-PVCs from benign RVOT-PVCs or MVT. METHODS: We evaluated the ventricular repolarization instability as assessed by the beat-to-beat T-wave amplitude variability (TAV) using Holter recordings in patients with RVOT-PVCs but with no structural heart disease. We determined the prematurity index, defined as the ratio of the coupling interval of the first ventricular tachycardia (VT) beat or isolated PVC to the preceding R-R interval just before the VT or isolated PVC in the Holter recordings. The study patients were classified into RVOT-PVCs/MVT (n = 33) and PVT/VF (n = 10). RESULTS: The two groups did not differ with respect to the age, sex, and left ventricular ejection fraction. There was no significant difference in the prematurity index between the two groups (RVOT-PVCs/MVT 0.66 ± 0.16 vs. PVT/VF 0.61 ± 0.13, P = 0.60). The patients with PVT/VF had a significantly larger maximum TAV than those with RVOT-PVCs/MVT (31 ± 13 vs. 68 ± 40 µV, P < 0.001). Patients with a higher than median value of the TAV (33 µV) were at increased risk of PVT/VF vs. those with a lower than median value, after adjusting for the age and sex [9.25 (95% confidence interval: 1.27-19.2); P = 0.03]. CONCLUSIONS: The TAV analysis is a useful measure to identify the subset of usually benign RVOT-PVC/MVT patients prone to PVT/VF.

BACKGROUND: Cardiac sarcoidosis (CS) generates myocardial scar and arrhythmogenic substrate. CS diagnosis according to the Japanese Ministry of Health and Welfare guidelines relies, among others, on cardiac magnetic resonance imaging with late gadolinium enhancement (CMR-LGE). However, access to CMR-LGE is limited. The electrocardiography-based Selvester QRS score has been validated for identifying myocardial scar in ischemic/nonischemic cardiomyopathy, but its efficacy has not been tested to evaluate CS. OBJECTIVE: The purpose of this study was to examine whether the QRS score can be applied to CS. METHODS: CS-associated myocardial scar was assessed by both CMR-LGE and QRS scoring in patients with extra-CS (n = 59). RESULTS: Of 59 patients, 35 (59%) were diagnosed with CS according to the Japanese Ministry of Health and Welfare guidelines. QRS-estimated scar mass positively correlated with that quantified by CMR-LGE (signal intensity ≥2SD above the reference; r = 0.68; P < .001). Receiver operating characteristic curves demonstrated optimal cutoffs of 9% CMR-LGE scar and 3-point QRS score to identify patients with CS. The areas under the curves of CMR-LGE and the QRS score were not significantly different (0.83 and 0.78, respectively; P = .27); both methods demonstrated similar diagnostic performance. A QRS score of ≥3 led to a higher incidence of CS-associated adverse events (death/fatal arrhythmia/heart failure hospitalization) than did a QRS score of <3 (35 ± 21 months of follow-up; P = .01). QRS score was an independent predictor of risk in multivariate analysis (P = .03). CONCLUSION: The Selvester QRS scoring estimates CS-associated myocardial damage and identifies patients with CS equally well as CMR-LGE. A higher QRS score is also associated with an increased risk of life-threatening events in CS, indicating its potential use as a risk predictor.

BACKGROUND AND PURPOSE: Many patients with atrial fibrillation (AF) and coronary artery stent deployment are given both antiplatelet drug and warfarin. Little information is available as to the relationship between the antithrombotic therapies in the late phase after stenting and the clinical outcomes of these patients. We examined the clinical outcomes of AF patients 12 months after coronary artery stenting. METHODS: We retrospectively examined 146 patients and classified them into three groups according to the antithrombotic therapies [dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT) plus warfarin, and DAPT plus warfarin] 12 months after stenting. We defined the primary endpoint as Thrombolysis in Myocardial Infarction major bleeding and the secondary endpoint as a composite of adverse events (CAE: all-cause death, nonfatal myocardial infarction, intracranial bleeding, and cerebral infarction). RESULTS: During a median follow-up of 37 months, major bleeding and CAE were observed in 14 (9.6%) and 46 (31.5%) patients, respectively. DAPT plus warfarin was an independent risk factor for major bleeding in a multivariate Cox hazard regression model after adjustment for age, gender, and the type of AF (hazard ratio: 4.20; 95% confidence interval: 1.13-17.27; p=0.033). No significant clinical variables were found for CAE. CONCLUSIONS: Prolonged use of DAPT with warfarin significantly increases the risk of major bleeding in AF patients after coronary artery stenting. Individualized antithrombotic treatment is required in these patients to prevent major bleeding.

BACKGROUND: Cardiac involvement is a leading cause of death from sarcoidosis. Because the efficacy of corticosteroid treatment is limited in patients with cardiac manifestation, early diagnosis is important. However, cardiac involvement is difficult to identify at early stages and is often underdiagnosed. Therefore, this study aimed to identify electrocardiographic risk factors for cardiac events in patients with extracardiac sarcoidosis. METHODS: This prospective observational cohort study included 227 patients with extracardiac sarcoidosis who did not have any cardiac manifestation (age, 49 ± 17 years; women, 63%). We studied the association of electrocardiographic abnormalities with developing cardiac manifestations. RESULTS: During a follow-up of 6.3 ± 3.7 years, 11 patients developed cardiac events, including advanced atrioventricular block (4 patients), ventricular tachycardia (4 patients), and systolic dysfunction (3 patients). All patients had electrocardiographic abnormalities prior to the development of cardiac events. In multivariate analyses, the baseline heart rate and PR interval were associated with increased risk of developing cardiac events. The QRS duration and corrected QT interval were not associated with cardiac manifestations. The multivariate analyses also revealed that baseline conduction disorder, ST segment/T wave abnormalities, and fragmented QRS complexes were associated with cardiac events. CONCLUSIONS: Electrocardiographic abnormalities occurred prior to cardiac events in extracardiac sarcoidosis. Patients with electrocardiographic abnormalities may require further evaluation for cardiac involvement and careful follow-up.

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for ischemic strokes, and making a robust risk stratification scheme would be important. Few studies have examined whether nonlinear dynamics of the heart rate could predict ischemic strokes in AF. We examined whether a novel complexity measurement of the heart rate variability called multiscale entropy (MSE) was a useful risk stratification measure of ischemic strokes in patients with permanent AF. METHODS AND RESULTS: We examined 173 consecutive patients (age 69 ± 11 years) with permanent AF who underwent 24-hour Holter electrocardiography from April 2005 to December 2006. We assessed several frequency ranges of the MSE and CHA2DS2-VASc score (1 point for congestive heart failure, hypertension, diabetes, vascular disease, an age 65 to 74 years, and a female sex and 2 points for an age ≥ 75 years and a stroke or transient ischemic attack). We found 22 (13%) incident ischemic strokes during a mean follow up of 3.8-years. The average value of the MSE in the very-low frequency subrange (90-300 s, MeanEnVLF2) was significantly higher in patients who developed ischemic strokes than in those who did not (0.68 ± 0.15 vs. 0.60±0.14, P<0.01). There was no significant difference in the C-statistic between the CHA2DS2-VASc score and MeanEnVLF2 (0.56; 95% confidence interval, 0.43-0.69 vs. 0.66; 95% confidence interval, 0.53-0.79). After an adjustment for the age, CHA2DS2-VASc score, and antithrombotic agent, a Cox hazard regression model revealed that the MeanEnVLF2 was an independent predictor of an ischemic stroke (hazard ratio per 1-SD increment, 1.80; 95% confidence interval, 1.17-2.07, P<0.01). CONCLUSION: The MeanEnVLF2 in 24-hour Holter electrocardiography is a useful risk stratification measure of ischemic strokes during the long-term follow-up in patients with permanent AF.

AIMS: We examined whether the severity of central sleep apnoea (CSA) and the level of C-reactive protein are associated with the prevalence and complexity of arrhythmias, and whether these factors contribute to increased risk of nocturnal sudden death. METHODS AND RESULTS: We prospectively examined 178 patients (age 70 ± 1 years) who were admitted to our hospital due to worsening heart failure. We recorded a simultaneous overnight cardiorespiratory polygraph and Holter ECG. Obstructive sleep apnoea was excluded and patients were dichotomized based on the median value of the central apnoea index (CAI) of 7.5/h. The prevalence and complexity of arrhythmias were compared between daytime (06:00 h to 15:00 h) and night-time (21:00 h to 06:00 h). A multivariate logistic regression analysis revealed that the CAI was associated with prevalence of atrial fibrillation (AF) [odds ratio 1.03, 95% confidence interval (CI) 1.02-2.51)] and sinus pause during the night-time period (1.12, 95% CI 1.08-1.35). The CAI and C-reactive protein were independently associated with non-sustained ventricular tachycardia during both daytime (1.22, 95% CI 1.00-6.92; and 5.82, 2.58-56.1, respectively) and night-time periods (3.57, 95% CI 1.06-13.1; and 10.7, 3.30-44.4, respectively). During a mean follow-up period of 22 months, 30 (17%) patients had cardiovascular deaths and the CSA was an independent predictor (hazard ratio 1.29, 95% CI 1.16-2.32); only 5 (2.8%) of them died due to ventricular tachyarrhythmia, occurring during wakefulness. CONCLUSIONS: We demonstrated that the severity of CSA and C-reactive protein levels are independently associated with the prevalence and complexity of arrhythmias. CSA was associated with increased mortality risk, but it was not related directly to nocturnal death due to ventricular tachyarrhythmia.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) are associated with significant mortality and morbidity. We sometimes encounter patients who have AF upon admission to the hospital, but it spontaneously converts to sinus rhythm within several days (i.e. converter). PURPOSE: We examined the association between the outcome and types of strategy for AF treatment in converters. METHODS: From January 2000 to December 2005, we identified 95 converters (age 69 ± 12 years) presenting with worsening HF and AF upon admission, in which sinus rhythm was restored within 7 days without either electrical or pharmacological cardioversion. The patients were classified into three groups according to the antiarrhythmic drug (AAD) therapy used: class I AAD, class III AAD, and rate-control drug. The patients were followed for 36 ± 23 months. RESULTS: The left ventricular ejection fraction (LVEF) significantly improved with conversion to sinus rhythm (38 ± 14% vs. 47 ± 13%, p<0.05). Those receiving class I AAD had a trend toward a well-preserved LVEF (50 ± 13%, n=35) as compared to those receiving class III AAD (43 ± 12%, n=24) or rate-control drug (47 ± 14%, n=36). In the patients receiving class I AAD, the rate of all-cause death increased 1.9-fold (p=0.009) compared to those receiving class III AAD, and 1.7-fold (p=0.010) compared to those taking rate-control drug. A hospitalization for HF was observed in 49 (52%) patients, however there was no significant difference in the rate of hospitalization among the three groups (p=0.890). Those receiving rate-control drugs had a 50% lower rate of the development of persistent AF than those taking class III AAD (p=0.019). CONCLUSIONS: A rate-control strategy should be the primary approach for converters to reduce mortality and development of persistent AF.

AIMS: Increased temporal repolarization lability, assessed by beat-to-beat variability of T-wave amplitude (TAV), has been shown to be associated with ventricular tachyarrhythmia in patients with a variety of clinical conditions. The aim of this study was to test the ability of TAV to identify patients presenting with malignant ventricular arrhythmia and to predict subsequent occurrences. METHODS AND RESULTS: We studied 20 consecutive patients (age 42 ± 15 years, mean ± standard deviation) presenting with ventricular tachyarrhythmia who did not have substantial underlying heart disease and compared them with 40 age- and sex-matched control subjects. The TAV was determined by Holter recording (Ela Medical). Patients with ventricular tachyarrhythmia had a higher maximum value of TAV (max TAV: 38 ± 18 vs. 22 ± 15 μV, P < 0.001) than did the controls. The sensitivity and specificity of max TAV > 22.4 μV for detecting the occurrence of ventricular tachyarrhythmia were 77 and 90%, respectively. During a mean follow-up period of 23 months, three patients had relapses of ventricular tachyarrhythmia. Patients with a recurrence of ventricular tachyarrhythmia had a trend towards a higher max TAV as compared with those who had ventricular tachyarrhythmia but did not relapse (56 ± 23 vs. 36 ± 16 μV, P = 0.061). CONCLUSION: Our results suggest that Holter-derived TAV might be associated with the occurrence and recurrence of ventricular tachyarrhythmia in patients without structural heart disease. Prospective validation will be necessary to assess the potential diagnostic value of the TAV in a large general population.

BACKGROUND: n-3 polyunsaturated fatty acids, primarily eicosapentaenoic acid (EPA), has been reported to have antiarrhythmic and antiinflammatory effects. The aim of the present study was to examine whether the combination of antiarrhythmic drugs and EPA reduced the frequency of atrial fibrillation (AF) in patients with paroxysmal AF. METHODS: We studied 50 patients with paroxysmal AF (age, 54 ± 9 years) after excluding the clinical conditions associated with an increased risk of AF. Patients were initially treated with antiarrhythmic drugs for 6 months (the observation period), and thereafter, EPA was added at a dose of 1.8 g/day for 6 months (the intervention period). During a one-year period, patients obtained an ECG recording using a portable device each morning and when arrhythmia-related symptom occurred. The end point was the difference of the AF burden (defined by the days of AF per month) between observation period and intervention period. Plasma EPA and C-reactive protein (CRP) levels were also determined. RESULTS: There was no significant difference in the AF burden before and after intervention (2.6 ± 2.2 days/months vs. 2.5 ± 2.2 days/months, P = 0.45). Although EPA level was significantly increased (42 ± 15 μg/mL to 120 ± 47 μg/mL, P < 0.001), CRP level was unchanged (1.04 ± 0.69 mg/L to 0.96 ± 0.56 mg/L, P = 0.24) following EPA treatment. CONCLUSIONS: Treatment of EPA in combination with antiarrhythmic drugs did not reduce the AF burden or the CRP levels in paroxysmal AF patients who had no evidence of substantial structural heart disease.

BACKGROUND: Prolonged duration of the QRS complex is a prognostic marker in patients with heart failure (HF), whereas electrocadiographic markers in HF with narrow QRS complex remain unclear. We evaluated the prognostic value of the T-wave amplitude in lead aVR in HF patients with narrow QRS complexes. METHODS: We examined 331 patients who were admitted to our hospital for worsening HF (68 ± 15 years, mean ± standard deviation) from January 2000 to October 2004 who had sinus rhythm and QRS complex <120 ms. The patients were categorized into three groups according to the peak T-wave amplitude from baseline in lead aVR: negative (<-0.1 mV; n = 209, 63%), flat (-0.1-0.1 mV; n = 64, 19%), and positive (>0.1 mV; n = 58, 18%). RESULTS: During a mean follow-up of 33 months, 113 (34%) patients had all-cause death, the primary end point. After adjusting for clinical covariates, flat T wave (hazard ratio [HR] 1.86, 95% confidence interval [CI] 1.42-2.46), and positive T wave (HR 6.76, 95% CI 3.92-11.8) were independent predictors of mortality, when negative T wave was considered a reference. CONCLUSIONS: As the peak T-wave amplitude in lead aVR becomes less negative, there was a progressive increase in mortality. The T wave in lead aVR provides prognostic information for risk stratification in HF patients with narrow QRS complexes.

BACKGROUND: The incidence of various cardiovascular diseases is known to exhibit seasonal variations, but seasonal patterns of paroxysmal atrial fibrillation (AF) have not been well characterized. OBJECTIVE: The objective of this study was to determine whether seasonal variation affects the incidence of paroxysmal AF and whether this pattern is affected by patient age. METHODS: We identified 258 paroxysmal AF episodes in 237 patients (age 65 +/- 14 years, mean +/- standard deviation; age range 16-95 years) among 12,390 consecutive 24-hour Holter electrocardiogram recordings obtained from 2001 to 2005 at our institute. Seasonal variations were analyzed by both month and by season. The relative risk (RR) of AF for each period was determined as being high or low in relation to the overall mean incidence. The association among clinical covariates and risk of paroxysmal AF was tested by logistic regression analysis. RESULTS: The incidence of paroxysmal AF was highest in September (RR = 1.40, 95% confidence interval [CI] 1.36-1.44) and lowest in June (RR = 0.52, 95% CI 0.50-0.54), with an RR difference of 63% (P < .001) among all patients. Patients aged > or =65 years demonstrated a peak incidence in September (RR = 1.46, 95% CI 1.41-1.51) and a minimum in June (RR = 0.55, 95% CI 0.52-0.58), while those aged <65 years showed a peak incidence in December (RR = 1.33, 95% CI 1.27-1.39) and a minimum in June (RR = 0.49, 95% CI 0.45-0.53). The incidence of paroxysmal AF also showed an autumn peak (RR = 1.21, 95% CI 1.16-1.27) and a summer minimum (RR = 0.66, 95% CI 0.62-0.70), with an RR difference of 53% (P < .001) among all patients. This seasonal variation in paroxysmal AF did not differ between patients of different age ranges. Clinical covariates including underlying disease or medications did not influence the monthly or seasonal variation in paroxysmal AF. There was a significant inverse relationship between the incidence of paroxysmal AF and the length of daylight in patients aged <65 years (r = -0.57, P < .05). CONCLUSION: There was a significant seasonal variation in paroxysmal AF, with maximum and minimum incidences in autumn and summer, respectively, and this pattern was not age dependent.